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P C Levendag

Publications and source records attributed to P C Levendag.

At least 19 recordsLinked to original sources

Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study.

PURPOSE: To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose-volume histograms (DVHs) were used. METHODS AND MATERIALS: From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system. RESULTS: Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs. CONCLUSIONS: The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.

Colon, Sigmoid

Identification of prognostic factors in patients with brain metastases: a review of 1292 patients.

PURPOSE: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials. MATERIALS AND METHODS: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports. RESULTS: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic factors in our material, although with lesser importance. In patients with lung primaries, sex was found to have significant impact on survival. In patients with breast primaries, interval between primary tumor and development of brain metastases appeared to be a statistically significant prognostic factor. Histology in patients with lung primaries and distribution of brain metastases were not found to be statistically significant in multivariate analysis. CONCLUSIONS: In this large database, the value of established prognostic factors was confirmed and, furthermore, some less well-recognized parameters such as response to steroid treatment, serum lactate dehydrogenase, age, sex in lung primaries, and site of primary tumor were established. From the three strongest prognostic factors--performance status, response to steroids, and evidence of systemic disease--simple identification of favorable and unfavorable subgroups of patients with brain metastases can be constructed.

Adolescent

Radiation-induced bilateral optic neuropathy in cancer of the nasopharynx. Case failure analysis and a review of the literature.

CASE REPORT: A case history of unanticipated radiation-induced bilateral optic neuropathy, 18 months after induction chemotherapy and radiation therapy for a locally advanced nasopharyngeal carcinoma, is presented. Retrospective reanalysis of the radiation therapy technique, with emphasis on the doses received by the optic pathway structures, was performed. These re-calculations revealed unexpectedly high doses in the range 79 to 82 Gy (cumulative external and brachytherapy dose) at the level of the optic nerves, which explained the observed radiation injury. CONCLUSION: Routine implementation of computed tomography for 3D dose planning purposes is therefore advocated. Review of the current literature confirms the importance of 3D dose planning in avoiding this complication and high-lights the role of MRI in establishing the diagnosis of radiation-induced optic neuropathy.

Adult

1H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration.

Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in 1H MR spectra of contrast-enhancing tumor at 5-10 min after Gd-contrast administration [Magn. Reson. Med. 37:222-225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0-5, 5-10, and/or 10-15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 +/- 3, 12 +/- 2, and 14 +/- 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.

Adult

Guidance of intracoronary radiation therapy based on dose-volume histograms derived from quantitative intravascular ultrasound.

Application of ionizing radiation to prevent restenosis in atherosclerotic vessels treated by balloon angioplasty is a new treatment under investigation in interventional cardiology and radiology. There is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of dose distribution over the arterial vessel wall. We present a new modality of dosimetry based on a method that three-dimensional (3-D) image reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) images. Dose volume histograms (DVH) are used to describe the cumulative distribution of dose over two specific volumes: i) at the level of the luminal surface, defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface, and ii) the adventitia volume is computed considering a 0.5-mm thickness from the echogenic media-adventitia interface. DVH provide a tool for reporting the actual delivered dose at the site believed to be the target: the adventitia, and to detect excessive radiation which could lead to vascular complications. Simulation of a gamma-emitter or of a radioactive source train in the center of the lumen are possible. The data obtained from the first ten patients included in the beta-irradiation trial (BERT 1.5) conducted in our institution are presented, supporting the use of DVH based on quantitative IVUS measurements for optimal dose prescription in vascular interventional radiation therapy.

Brachytherapy

Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx.

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.

Adult

Field margin reduction using intensity-modulated x-ray beams formed with a multileaf collimator.

PURPOSE: In axial, coplanar treatments with multiple fields, the superior and inferior ends of a planning target volume (PTV) are at risk to get underdosed due to the overlapping penumbras of all treatment fields. We have investigated a technique using intensity modulated x-ray beams that allows the use of small margins for definition of the superior and inferior field borders while still reaching a minimum PTV-dose of 95% of the isocenter dose. METHODS AND MATERIALS: The applied intensity modulated beams, generated with a multileaf collimator, include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and inferior ends of the PTV. The benefits of this technique have been assessed using 3D treatment plans for 10 prostate cancer patients. Treatment planning was performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations for the narrow boost fields have been compared with measurements. The application of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix Medical AB), which allows fully computer-controlled setup of all involved treatment fields. RESULTS: Compared to our standard technique, the superior-inferior field length can be reduced by 1.6 cm, generally yielding smaller volumes of rectum and bladder in the high dose region. For the narrow boost fields, calculated relative dose distributions agree within 2% or 0.2 cm with measured dose distributions. For accurate monitor unit calculations, the phantom scatter table used in the Cadplan system had to be modified using measured data for square fields smaller than 4 x 4 cm2. The extra time needed at the MM50 for the setup and delivery of the boost fields is usually about 1 min. CONCLUSION: The proposed use of intensity modulated beams yields improved conformal dose distributions for treatment of prostate cancer patients with a superior-inferior field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit from the application of the boost fields.

Humans

Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate.

PURPOSE: Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP). METHODS AND MATERIALS: Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr.HDR, which entailed twice-daily fractions of > or = 3 Gy. The other 19 patients were administered PDR, which consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients treated by brachytherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77). RESULTS: Excellent locoregional control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response relationships were established, significant, however, only for the BEDcor10 (p = 0.03). CONCLUSION: The 3-year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.

Brachytherapy

Spatial temperature control with a 27 MHz current source interstitial hyperthermia system.

PURPOSE: This article gives an overview of the properties of a 27 MHz current source interstitial hyperthermia system, affecting temperature uniformity. METHODS AND MATERIALS: Applicators can be inserted in standard flexible afterloading catheters. Maximum temperatures are measured with seven-point constantan-manganin thermocouple probes inside each applicator. Temperature can be controlled automatically using a simple control algorithm. Three-dimensional power absorption and thermal models for inhomogeneous tissues are available to optimize applicator geometry and phase configuration. Properties of the interstitial heating system have been verified both in phantom experiments and in in vivo treatments of rhabdomyosarcomas implanted in the flank of a rat. RESULTS: An experiment with four electrodes in one catheter proves that longitudinal control of the specific absorption rate (SAR) is feasible. Local cooling applied by cold water circulation through a catheter perpendicular to the afterloading catheter could be compensated by independent control of electrode power. Furthermore, comparison of two different phase configurations using four dual electrode applicators shows that the SAR distribution can be manipulated significantly, utilizing the phase of the electrodes. Finally, the temperature can be controlled safely and model calculations are in fair agreement with the measurements. CONCLUSIONS: The features of the 27 MHz current source interstitial hyperthermia system enable spatial temperature control at approximately 1.5 cm.

Animals

A new applicator design for endocavitary brachytherapy of cancer in the nasopharynx.

INTRODUCTION: In attempting to improve local tumor control by higher doses of radiation, there has been a resurgence of interest in the implementation of brachytherapy in the management of primary and recurrent cancers of the nasopharynx. Brachytherapy with its steep dose fall-off is of particular interest because of the proximity of critical dose limiting structures. Recent developments in brachytherapy, such as the introduction of pulsed-dose-rate and high-dose-rate computerized afterloaders, have encouraged further evolution of brachytherapy techniques. MATERIALS AND METHODS: We have designed an inexpensive, re-usable and flexible silicone applicator, tailored to the shape of the soft tissues of the nasopharynx, which can be used with either low-dose-rate brachytherapy or high (pulsed)-dose-rate remote controlled afterloaders. RESULTS AND CONCLUSIONS: This Rotterdam nasopharynx applicator proved to be easy to introduce, patient friendly and can remain in situ for the duration of the treatment (2-6 days). The design, technique of application and the first consecutive 5 years of clinical experience in using this applicator are presented.

Brachytherapy

Reconstruction accuracy of a dedicated localiser for filmless planning in intra-operative brachytherapy.

BACKGROUND AND PURPOSE: With the use of HDR and PDR afterloaders containing a single stepping source, brachytherapy dose distributions can be optimised by varying the source dwell time. With the goal of implementing 'conformal brachytherapy', i.e. ensuring that the dose distribution conforms as accurately as possible to the target volume, we evaluated a set-up which enabled on-line implant localisation and dose planning during implantation. MATERIALS AND METHODS: The set-up, designated as an integrated brachytherapy unit (IBU), consists of a shielded operating room equipped with an HDR afterloader and a dedicated brachytherapy localiser connected to a treatment planning computer. The localiser is isocentric and has an extra degree of freedom in comparison to conventional simulators (i.e. an L-arm in combination with a C-arm) and enables viewing of the implant from any direction. A reconstruction algorithm which takes into account both rotation axes, i.e. the L-arm and C-arm angle, was developed for the localiser. The reconstruction procedure was tested by using the IBU localiser to measure the reconstruction accuracy with a phantom (containing 25 markers at well defined positions) and using reconstruction from radiographs. These results were compared to simulations where the accuracy of reconstruction was determined as a function of the reconstruction angle and the accuracy of read-outs of the localiser settings. On-line localisation and dose planning during implantation is based on filmless planning, i.e. fluoroscopy images and the corresponding localiser settings are imported into the treatment planning computer during implantation. The accuracy of filmless planning was determined using fluoroscopy images in the same set-up as for the experiments with the radiographs. The effect of reconstruction inaccuracies on the total irradiation time and the dose in target or normal tissue points was elucidated for clinically relevant implant geometries. The treatment plans of two phantoms based on reconstruction from films as well as fluoroscopy images were compared with plans for implants defined by exact co-ordinates. RESULTS: The average reconstruction error due to the accuracy of the read-out of the localiser settings varied between -0.18 and 0.24 mm, with a standard deviation (arising from digitisation errors) ranging from 0.11 to 0.22 mm. Using filmless reconstruction and the 10 inch field of view of the image intensifier (without applying correction for the geometric distortions) the average reconstruction error ranged from 0.01 to 0.65 mm, and the standard deviation ranged from 0.40 to 0.73 mm. These errors arose as a consequence of the finite pixel size and geometric distortions. These limited errors did not influence the treatment time for clinical implant geometries and had only a minor effect (<1%) on the dose in markers during filmless planning. CONCLUSION: This IBU set-up, with a dedicated brachytherapy localiser, allows for a rapid and accurate filmless planning procedure based on implant localisation from fluoroscopy images.

Brachytherapy

Design of applicators for a 27 MHz multielectrode current source interstitial hyperthermia system; impedance matching and effective power.

In interstitial heating one of the main requirements for achieving a certain elevated temperature in a tumour is that the effective power per applicator (Peff), i.e. the power which is actually deposited in the tissue, is sufficiently high. In this paper this requirement is discussed for the applicators of the 27 MHz multielectrode current source (MECS) interstitial hyperthermia (IHT) system. To minimize power reflection, the applicator impedance was matched with the generator impedance by adjusting the length of the coaxial cable in between. Transmission line losses, applicator efficiency and subsequently Peff were computed for several applicator types. The actual Peff per electrode was obtained from calorimetric measurements. Experiments with RC loads, which can be seen as perfect applicators, were performed to investigate the effect of mismatching on Peff. Applicator losses were measured for clinically used applicators, both single- and dual-electrode, utilizing saline phantoms. A simple spherical tumour model, using the effective heat conductivity (keff) to account for heat transport, was used to estimate Peff for a given tumour size, implant size and applicator density. Computations of Peff of various MECS-IHT electrodes were in close agreement with the phantom measurements. Most of the initial generator power was absorbed in the transmission line (60-65%). The efficiency of the applicators was about 65%. For both single- and dual-electrode applicators the effective electrode power was found to be about 1 W. Model calculations show that Peff of 1 W is sufficient to reach a minimum tumour temperature of 43 degrees C in well perfused tumours (keff = 3 W m-1 degree C-1), using a typical implant with 2 cm electrodes and 1.5 cm spacing. Mismatching can considerably affect Peff. Both a reduction to almost zero and a two-fold increase are possible. However, because the matching theory is well understood, mismatching is not a serious problem in clinical practice and can even be used to increase Peff if necessary. We conclude that the applicator design and the impedance matching method chosen in the MECS system allow heating to temperatures in the therapeutic range with implants used in clinical practice.

Biophysical Phenomena

The history of radiotherapy in The Netherlands.

Soon after the discovery of x-rays by W. C. Roentgen in 1895, a publication on fluoroscopy and x-ray pictures/films appeared in the Dutch medical literature in February 1896. The present article reviews the subsequent developments in the field of therapeutic radiology in The Netherlands and, in particular, the evolution of radiation oncology as a distinct medical specialty.

History, 19th Century

A quality control study of the accuracy of patient positioning in irradiation of pelvic fields.

PURPOSE: Determining and improving the accuracy of patient positioning in pelvic fields. METHODS AND MATERIALS: Small pelvic fields were studied in 16 patients treated for urological cancers using a three-field isocentric technique. Large pelvic fields were studied in 17 gynecological cancer patients treated with anterior and posterior (AP-PA) parallel opposed fields. Quantitative analysis of 645 megavolt images and comparison to 82 simulation images were carried out. RESULTS: Small pelvic fields: for the position of the patient in the field, standard deviations of the difference between simulation (SIM) and treatment (MV) images were 3.4 mm in the lateral direction, 5.3 mm in the cranio-caudal direction, and 4.8 mm in the ventro-dorsal direction. Alterations in the positioning technique were made and tested. Large pelvic fields: differences between simulation and treatment images for the position of the patient in the field were 4 mm [1 standard deviation (SD)] in the lateral direction and 6.5 mm in the cranio-caudal direction. A systematic shift of the treatment field in the cranial direction had occurred in the majority of patients. A positioning technique using laser lines and marking of the caudal field border was shown to be more accurate. CONCLUSIONS: Studies of positioning accuracy in routine irradiation techniques are needed to obtain data for definition of the margins for each treatment site at each institution. Random variations should be kept at a minimum by monitoring and improving positioning techniques. Treatment verification by megavolt imaging or film should be used to detect and correct systematic variations early in the treatment series.

Endometrial Neoplasms

Pulsed dose rate and fractionated high dose rate brachytherapy: choice of brachytherapy schedules to replace low dose rate treatments.

PURPOSE: Pulsed dose rate (PDR) brachytherapy is a new type of afterloading brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is simulated by a series of "pulses," i.e., fractions of short duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Hoed Cancer Center, the term "PDR brachytherapy" is used for treatment schedules with a large number of fractions (at least four per day), while the term "fractionated high dose rate (HDR) brachytherapy" is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can be applied as alternatives for LDR BT. This article deals with the choice between PDR and fractionated HDR schedules and proposes possible fractionation schedules. METHODS AND MATERIALS: To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete repair formulation as given by Brenner and Hall, and by Thames. In contrast to earlier applications of this model, both the total physical dose and the overall time were not kept identical for LDR and HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy (ERT) and for BT applications as a single treatment. Because the knowledge of both alpha/beta values and the half time for repair of sublethal damage (T 1/2), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatments have been performed for a wide range of values of alpha/beta and T 1/2. The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. RESULTS: If the condition that total physical dose and overall time of a PDR treatment must be exactly identical to the values for the corresponding LDR treatment regimen is not applied, there appears to be less need for strong fractionation in PDR schedules. If the overall time is at least as long as that of the LDR schedule and if the total physical dose is (slightly) adapted, PDR schedules can be designed using longer pulse intervals of up to 3 h. Schedules with sufficiently long intervals have significant logistic advantages in terms of patient care and treatment tolerance. However, in general, PDR schedules that apply more fractionation have a lower risk of overdosing normal tissues in comparison to fractionated HDR schedules. Applying probable ranges for the values of alpha/beta and T 1/2, the model calculations indicate that the differences in effects between the proposed fractionated HDR and PDR schedules could be rather small. To detect the magnitude of these differences, (randomized) clinical studies with rather large patient groups might be needed. CONCLUSIONS: Pulsed dose rate treatment schedules with longer intervals of up to 3 h appear adequate to replace LDR treatment schedules. Whether PDR schedules can, indeed, replace LDR treatment schedules and whether they offer detectable advantages over schedules with less fractionation (fractionated HDR) should be tested in clinical studies.

Brachytherapy

1H MR spectroscopy detection of lipids and lactate in metastatic brain tumors.

1H MR spectroscopy was used to correlate the metabolite signals in 66 untreated metastatic brain tumors with the results of Gd-DTPA enhanced MRI. Cubic volumes containing brain metastases of lung cancer (n = 17), mammary carcinoma (n = 24), melanoma (n = 12) and those originating from other tumors (n = 13) were examined using the double spin echo technique with CHESS pulses for water suppression and TE = 135 ms. Apart from trends toward reduced signals of choline-containing compounds (Cho) and reduced post-Gd MRI contrast in lung cancer compared with the other pathology groups, the four tumor groups had similar MRI and MRS characteristics. Metastases without lipid or lactate (Lact) signal in the 1H MR spectra were comparatively small in size with homogeneous post-Gd MRI enhancement (33 +/- 5%, means +/- SEM; n = 24) and elevated Cho signals compared with normal contralateral brain tissue (70 +/- 5% of contralateral N-acetyl aspartate signal; p < 0.001). The other metastases showed either unambiguous lipid signals (n = 30) or MRS detectable Lact (n = 12) and were heterogeneous on MRI with divergent signals of Gd-enhancement (49 +/- 5% vs 14 +/- 8%, p < 0.001) and Cho (88 +/- 10 vs 47 +/- 8% of contralateral NAA; p = 0.02). Those with Lact were significantly larger compared with both other groups (p < 0.02, both). It is concluded that brain metastases can be categorized into early stage (Cho), intermediate stage (lipid, higher Cho) and late stage metastases (Lact, lower Cho).

Brain Neoplasms